These studies focus upon the serotonergic neurons of the forebrain, whose cell bodies lie in the dorsal and median raphe nuclei. Selective chemical lesions will be used to destroy portions of this ascending neuronal system. We use rotational behavior after unilateral lesions as one index of dopamine function which is released by serotonin lesions, also with bilateral serotonin lesions, spontaneous motor activity and response to amphetamine is changed. Since there is evidence that benzodiazapine effects on myoclonic seizures are mediated by 5-HT receptors, we will also study the effects of diazepam and other benzodiazepines on myoclonics after raphe lsions, using both 5-HTP induced myoclonus and that produced by o,p-DDT. We are also studying the recovery of function which occurs after selective lesions of the median raphe nucleus. Since this recovery is reversible with PCPA (a blocker of serotonin synthesis) it seems to depend upon restoration of 5-HT neuronal function, most likely in the substantia nigra.